Effects of interferon gamma on native human acute myelogenous leukaemia cells

Cancer Immunology, Immunotherapy : CII
Elisabeth ErsvaerØystein Bruserud

Abstract

T cell targeting immunotherapy is now considered a possible strategy in acute myelogenous leukaemia (AML), and IFNgamma release may then contribute to the antileukaemic effects. We investigated the effects of IFNgamma on native human AML cells. Normal T cells could be activated to release IFNgamma in the presence of AML cells. Furthermore, high levels of CD119 (IFNgamma receptor alpha chain) expression were observed for all 39 patients examined. Receptor expression was decreased after exposure to exogenous IFNgamma, and receptor ligation caused Stat1 phosphorylation but no phosphorylation of the alternative messengers Erk1/2. The effect of exogenous IFNgamma on AML blast proliferation was dependent on the local cytokine network and IFNgamma (1) inhibited proliferation in the presence of exogenous IL1beta, GM-CSF, G-CSF and SCF; (2) had divergent effects in the presence of IL3 and Flt3 (65 patients examined); (3) inhibited proliferation in the presence of endothelial cells but had divergent effects in the presence of fibroblasts, osteoblasts and normal stromal cells (65 patients examined). IFNgamma increased stress-induced (spontaneous) in vitro apoptosis as well as cytarabine-induced apoptosis only for a subset of patients. Fur...Continue Reading

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Citations

Feb 18, 2011·Cancer Immunology, Immunotherapy : CII·Sally M AmosMichael H Kershaw
Feb 11, 2009·Blood·Dirk Schmidt-ArrasFrank-D Böhmer
Sep 5, 2014·Blood·Alexander M de BruinMartijn A Nolte
Apr 29, 2020·Scientific Reports·Maira da Costa CacemiroFabíola Attié de Castro
May 24, 2020·Journal of Clinical Medicine·Alice PievaniMarta Serafini
Oct 28, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·JongBok LeeLi Zhang
Dec 4, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chindu GovindarajMagdalena Plebanski

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